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alzheimer's disease (science) > Everything > Flashcards

Everything Flashcards

1
Q

What Medronic device for chronic pain was approved in March 2019?

A

Medronic received FDA clearance for its Accurian radiofrequency ablation system for nerve tissues (treatment for chronic pain)

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2
Q

What are the 3 elements of cash flow?

A

Cash from operations, Fixed assets purchases (PP&E), Financing activities (net borrowings, income tax, sale of stock)

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3
Q

What is cash from operations? What are the two components of cash from operations?

A

Separate section related to cash flow from operating activities (cash receipts - cash disbursements)

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4
Q

What is net income equation?

A

Net income = Sales - cost & expenses + non operating income - non operating expenses

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5
Q

What makes an animal a mammal?

A

Remember W-H-A-L-E. W- Warm blooded, H-Hair, A-Air-breathing, L- Live births, E-Eats or drinks milk

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6
Q

What are two terms for shareholder’s equity?

A

“Net worth” and “book value”

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7
Q

What are good therapeutic recruiter firms?

A

Klein Hersh, Accertitute, Catalyst Advisors

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8
Q

What is the mechanism of Tecfidera (chemical?) and what were sales in 2018?

A

Biogen’s Tecfidera (dimethyl fumarate) is approved for MS and brought in $4.27B in 2018 revenue. They found that Tecfidera hyper “methylates” a genomic site in CD4 T-cells that encodes miR-21, a microRNA critical for producing MS-related T-cells

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9
Q

What is function of fascin-1 and what does inhibition of fascin-1 result in?

A

Fascin-1 is an actin bundling protein and inhibiting fascin-1 allows for synaptic generation in AD mice (Spinogenix)

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10
Q

What is the prevalence of Alzheimer’s in US and WW now and expected in 2050? What areas (2) is AD most prevalent and (1) least prevalent?

A

Affects 5M in US, 50M WW (2018), Expected 14M in US and 130M WW by 2050. Prevalence is highest in North Africa and Middle East and least common in Europe.

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11
Q

Costs vs. expenses vs. expenditures

A

Costs are money paid to making the product (usually includes labor and material), expenses include money used to develop it, sell it, account for it, etc. These both become expenditures when money is sent out to vendors to pay for it.

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12
Q

What is the function of APOE?

A

APOE shuttles cholesterol and other lipids between cells.

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13
Q

What is the process of inventory to cash?

A

Finished goods inventory is sold, it becomes an “accounts receivable”, once customer pays - cash

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14
Q

What is Fast Fourier transform (FFT) and why is it used? What is the most common algorithm of FFT used?

A

This is the most commonly used method for transforming time-varying signal to frequency domain because running time is very slow for discrete fourier transform (since algorithm is quadratic to signal size T). Most common algorithm of FFT is Cooley-Tukey algorithm, which uses divide and conquer strategy to break down DFT into many smaller DFTs.

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15
Q

What are alpha waves? What frequency? What functions are they involved in?

A

8-12Hz waves suggest brain idling and are indicative of inattentive states or consciously practicing meditation

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16
Q

How does abeta levels and APOE4 status affect cognitive decline inflection point age?

A

Abeta negative - 78.8 years old
Only Abeta - 69.4 years old
Abeta/APOE4 - 65 years old

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17
Q

What is normal board member frequency? How many times/year? For early and more mature companies?

A

7.9 meetings/year average

1/month for early companies, 1/2months when more mature

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18
Q

How much did Cadent Therapeutics raise and from who in November 2018?

A

Cadent Therapeutics raised a $40M Series B led by Cowen Healthcare Partners and Atlas, with participation from QiMing Venture Partners and Novartis Institute for Biomedical Research.

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19
Q

What is “income taxes paid”?

A

Taxes that are actually paid to the government, doesn’t get put on cash flow statement until actually paid

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20
Q

GeNeuro (March 2019)

A

Geneva based public company, temelimab in MS (just finished Phase 2b study) - extension study had compelling data, temelimab in CIDP (chronic immunoflammatory demyelination polyneuropathy) - Phase 1, Anti-HERV-W mAb for inflammatory psychosis, Anti-HERV-K mAb for ALS

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21
Q

What is Retained Earnings? When a company has not made a profit, what is the term for retained earnings?

A

All of the company’s profits that have not been returned to shareholders as dividends. Sum of profits - sum of dividends; This is pool of money that can be used to pay out future dividends. “Negative retained earnings” for company with no profit.

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22
Q

What was the deal between Akili and Shionogi in March 2019?

A

Akili Interactive made a deal with Shionogi to bring their digital therapeutics to Japan in $20M upfront payment and $105M in potential milestones

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23
Q

What rate are taxes?

A

34% on pre-taxes income

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24
Q

What type of somatic recombination of APP was discovered and in what lab?

A

Somatic recombination of APP occurs mosaically as thousands of various genomic cDNA (gencDNA) which included copies that lacked introns or contained intra-exonic junctions, insertions, deletions or SNPs in AD brains. This was discvoered by Jerold Chun in Sanford in La Jolla, CA

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25
Q

How much did EIP Pharma raise and from whom in May 2018? What is their program and where did they get it from?

A

EIP raised a $20M Series B round from Access Industries. They have neflamapimod (p38a inhibitor) from Vertex for AD

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26
Q

Cash flow (2 types)

A

Cash flow positive - when cash at end of period is greater than cash at beginning of period; Cash flow negative - when cash at end of period is less than cash at beginning of period

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27
Q

What is a myocardial infarction? What happens biologically to cause one?

A

Heart attack. Cardiac ischemia occurs when the heart is starved of oxygen by blockage of coronary arteries delivering it to the heart. If this cardiac ischemia lasts too long, the starved heart tissue dies.

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28
Q

What components related to cholesterol (2 studied) when allosterically activated could enhance pTau degradation independent of APP and Abeta? What drug could do this and what is it typically used for? Who’s lab was this discovered?

A
  1. Cholesteryl ester (CE) or downstream (CYP46A1). CYP46A1-CE-tau is a druggable axis. Efavirenz (inhibitor of reverse transcriptase of HIV-1 virus). Laurence Goldstein from UCSD.
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29
Q

What is a Multiunit hash (neural hash)?

A

Signal recorded by an extracellular electrode implanted in the brain that is a mixture of signals from several neighboring neurons, with sounds from closer neurons producing larger amplitude deflections in the recorded signal

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30
Q

What are Cost of goods sold (COGS) and when does it get recorded on income statement?

A

What you spend when you buy or make products for inventory; only when inventory is sold does its value move from balance sheet to income statement

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31
Q

Liquidation preference (definition)

A

If a startup liquidates or is acquired, then VC gets back amount they invested or a multiple of that amount before other shareholders (more centrally here, the founders). Liquid preference refers to both preference and the participation.

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32
Q

What is accrual vs. cash basis?

A

“Operating on an accrual basis” - when income and expenses are measured when transactions occur; “Operating on an cash basis” - measuring when cash is received or spent

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33
Q

What is a non-cash transaction? What is an example?

A

A transaction where cash is not exchanged. Have no effect on cash flow statement, but do affect income statement and balance sheet. An example is when goods are shipped to customer, no cash is exchanged in the transaction proper, customer pays later

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34
Q

What happens to mitophagy in AD patients? What specific mitophagy markers are affected?

A

Neuronal mitochondria are smaller and show excessive damage in AD postmortem hippocampal regions. Basal levels of mitophagy were 30-50% lower in AD hippocampus and phosphorylation of key mitophagy markers (TBK1 and ULK1) were reduced in AD iPSCs

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35
Q

What cetaceans are toothed (4)?

A

Toothed cetaceans include dolphins, porpoises, and whales such as the beaked and sperm whales

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36
Q

What is a company consequence if aducanumab is approved?

A

Companies will need to pay for aducanumab as SOC.

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37
Q

What effect does IFN-g have on microglia

A

IFN-g may be able to prime microglia which results in reduced gamma oscillation frequency of 8 Hz. IFN-g results in changes in microglia morphology, expansion and upregulation in MHC-II, CD-86, IL-6, i-NOS, but not TNF-a

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38
Q

What is the underside of a whale’s tail called? Why is it special?

A

The underneath of a whale’s tail (called the fluke) is like a fingerprint, it is unique to every whale.

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39
Q

What are 4 lifestyle risks for AD?

A
  1. Depression
  2. Low education
  3. Obesity
  4. Diabetes
  5. Smoking
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40
Q

Who is Miles Davis? What jobs did he have (3)?

A

American jazz trumpeter, bandleader, and composer who was among the most influential and acclaimed figures in the history of jazz and 20th century music.

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41
Q

Statement of changes in financial position - what is it? What 3 components?

A

“Bridge” between cash from beginning of period to cash from end of period; 1. Cash flow from operations 2. Cash flow from investing (PP&E) 3. Cash flow from financing (selling stock, borrowing money, paying out dividends)

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42
Q

Orders vs. shipments

A

Orders do not affect financial statements and are when order is placed by customer, shipment is when the item is actually shipped (shipments is equivalent to sales)

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43
Q

How much did Axial Therapeutics raise and from who in March 2019?

A

Axial Therapeutics raised a $25M Series B round led by Serverture Partners with Domain Associates, Longwood Fund and Heritage Medical Systems participating

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44
Q

Karuna Pharmaceuticals raise, who when, how much?

A

Raised $42M (August 2018) from ARCH, Wellcome Trust, PureTech Health and Steven Paul

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45
Q

What are fixed assets purchases?

A

Total cash paid for fixed assets paid in the period (PP&E - property, plant, and equipment)

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46
Q

How does cash basis affect relationship between income and cash flow statements?

A

They are the same.

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47
Q

What diseases and what percentage of cases is TDP-43 a player?

A

97% of ALS cases, 45% of FTD, 60% of AD, 60% of chronic traumatic encephalophathy (CTE)

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48
Q

Sage Therapeutics

A

Sage Therapeutics has a pipeline of GABA modulators; brexanalone is being evaluated by FDA for PPD, 2 Phase 3 drugs for MDD and PPD and a number of early stage drugs in insomnia, bipolar depression, PD and essential tremor

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49
Q

Who is the writer of Hamilton?

A

Lin-Manuel Miranda

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50
Q

What is second basic equation of accounting?

A

Sales - cost & expenses = income

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51
Q

What is an estuary?

A

Estuary is a body of brackish water with rivers flowing into it that meets the open ocean. It is a transition zone of salt and fresh water.

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52
Q

What is ECoG? What are the advantages of ECoG vs. EEG (4)?

A

Electrocorticography - Technique for recording brain signals that involve placing 1-8 Surface electrodes (2-5mm in diameter) that are surgically placed on the surface of the brain in a grid with a distance of 10mm to 1cm apart and record electrical activity from 10,000s of neurons underneath. Advantages: Has great spatial (tenths of mm vs. cm with EEG), great bandwidth range (0-200Hz vs. 0-40Hz) and greater amplitude (50-100uV vs. 10s of uV), therefore less artifacts due to muscle activity and ambient noise.

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53
Q

What is fMRI? What does it measure and what are its advantages?

A

Functional magnetic resonance imaging - Non-invasive device that measures changes in blood flow to different regions in the brain (measures BOLD - blood oxygenated level dependent activity). Great spatial resolution (1-3mm), but poor temporal resolution (measurements start 100s of ms after neural activity, peak at 3-6s and end at 20s)

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54
Q

What is total liabilities equation?

A

Sum of current liabilities and long term debt

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55
Q

Pacira Pharmaceuticals

A

Exparel (bupivicaine liposomal suspension injection) - local non-opiod analgesic administered at the surgery that results in reduced pain and reduced opiod use for acute post surgical pain

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56
Q

Who is Michael Kahn? How many nominations and times did he win an academy award? Name 5 of his works.

A

Most respected film editor. 8 nominations and 3 winning academy awards. Editor of Saving Private Ryan, Raiders of the lost ark, Schindler’s list, Lincoln, and almost all of Steven Spielberg’s movies.

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57
Q

Where is Bilal Zubera a partner?

A

Lux Capital

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58
Q

What percentage of cases have mutations (3) in AD and what are they? What are two genes that are risk factors for AD?

A

Around 1% of AD cases are mutations in APP, PSEN1, or PSEN2. Certain mutations in APOE and TREM2 can increase risk of developing AD.

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59
Q

What is a flexible array made of and why is it better?

A

Microelectrodes made of polyimide, parylene, benzocyclobutene rather than silicon which provides a better match to mechanical properties of brain and reduces inflammation

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60
Q

Who did Pacira Pharmaceuticals acquire in March 2019 and what was payment?

A

Pacira Pharmaceuticals acquired Myoscience (Ionerva - device that injects nitrous oxide to freeze nerves which gives 3 month relief from pain while nerves regenerate for chronic pain) for an upfront payment of $120M and $100M in potential milestones. Should close in April.

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61
Q

Learning how to learn process (1-3 days) (3)?

A
  1. Read books - skimmed style (Read introduction, conclusion, read first paragraph of each chapter, read 1-2 pages of each chapter, read first sentence of each paragraph)
  2. Deconstruct skills
  3. Identify obstacles and ways to overcome them
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62
Q

What are the 2 spike sorting methods and what do they measure?

A

Simple - Classify spikes according tp peak amplitude
Window discriminator method - experimenter visually examines data and places windows on aligned recordings of spikes of the same shape, method then assigns all future spikes crossing one or more of these windows to the same neuron

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63
Q

What is a neurochip and what does it do?

A

A neurochip is a closed-loop battery operated system containing electrodes that is surgically implanted in the brain to record one or more neurons, performs signal processing and other computation on-board the chip, based on signals delivers stimulation to appropriate neurons.

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64
Q

What does a cash flow statement show?

A

Cash flow statement shows the movement of cash within a given period. Cash at beginning of period + Cash brought it - Cash spent = Cash at end of period

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65
Q

What is standard cost?

A

Cost/item for manufacturing cost

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66
Q

What types of things does the shareholder representative deal with?

A
  1. Escrow
  2. Working capital adjustments
  3. Litigation
  4. Earn outs
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67
Q

Why is the ocean green or blue?

A

If the ocean is green, it has tons of life and micro-organisms, if the water is crystal blue, not much life.

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68
Q

What was the Abcellera/Denali deal in March 2019?

A

Denali has the opt in option for antibodies developed for 8 targets for neurodegneration using Abcellera’s microfluidic platform. Abcellera’s antibodies from partnership in 2015 are now in Denali’s preclinical development

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69
Q

How much did Apello Pharmaceuticals raise and from who in June 2018? What programs do they have and where did it come from?

A

Apello raised $10.5M Series A from Deerfield Management and Mountain Group Partners. They have a positive allosteric modulator of metabotropic glutamate receptor subtype 4 (which controls glutamate and GABA transmission in the brain) for PD. Licensed from Vanderbilt University’s Center for Neuroscience Drug Discovery

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70
Q

What is tardive dyskenisia?

A

Side effect of antipsychotic drugs (inhibiting dopamine) - leads to stiff, jerky muscle movements of your face and body that you can’t control

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71
Q

What do you need if you want to do an interim analysis?

A

You need to write it in your protocol

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72
Q

Karuna Pharmaceuticals (Programs and how it relates to Eli Lilly)

A

Karuna Pharmaceuticals is developing KarXT- xenomeline (M1/M4 muscarinic receptor agonist) + trospium chloride (muscarinic receptor antagonist that doesn’t enter CNS). Eli Lilly was developing xanomeline in the 1990s, but had to stop Phase 2 trial due to >50% drop out rate due to side effects.

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73
Q

What are crampons?

A

Grid of 2-inch steel spikes clamped to the sole of your shoe to gain traction in the snow

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74
Q

Axial Therapeutics (March 2019)

A

Targeting gut-brain axis (microbiome play) in PD and Autism (Phase 1 in PD and expected to enter Phase 1b/2a in adolescent ASD in 1Q2019)

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75
Q

What is an early marker of AD pathology that correlates with cognitive decline related to tau? Where has it been shown to accumulate?

A

pThr231 Tau, shown to accumulate in APP duplication iPSC-derived FAD neurons.

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76
Q

What is the MMSE test and what is its accuracy, sensitivity and specificity?

A

10 minute paper and pencil assessment. 82% accurate with 80% sensitivity and 94% specificity

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77
Q

Fourier analysis allows input signals to be translated into ______ and then _______. What feature does this then allow you to do? Give an example of this feature.

A

Amplitude, dominant frequency. Filtering. EEG signals are often corrupted by “line noise” around 60 Hz due to AC power supply, you can use a “notch” filter to remove 60 Hz frequency component of signal

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78
Q

What does xerophytic mean?

A

Species of plant that has adaptations to survive in an environment with little liquid water, such as a desert or an ice or snow-covered region in the Alps or the Arctic.

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79
Q

What is the role of T-cells in MS?

A

MS happens when brain homing T-cells mistakenly attack the CNS.

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80
Q

If there is a down round, what can be done to founder’s equity for round and how can it be structured?

A

Option pool should needs to be increased if founders will get diluted in order to incentivize them, good to make milestone based (vesting) close to original amount

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81
Q

What are net borrowings?

A

Cash paid to pay off loans or dividends or cash brought in from loans

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82
Q

What was the deal between Axovant and Oxford Biomedica in 2018? What effect did therapy have in 2019?

A

Axovant bought AXO-Lenti-PD (gene therapy for 3 genes - Tyrosine hydroxylase, aromatic L-amino acid decarboxylase, cyclohydrolase 1 - enzymes crucial for dopamine synthesis) - for $30M upfront payment. 2 Patients showed improvement on UPDRS.

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83
Q

What is shareholder’s equity? What are the two equations? What are the 2 ways each to increase/decrease shareholder’s equity?

A

Shareholder’s equity is any money coming into the company - it consists of capital stock + retained earnings. Also, total assets - total
liabilities. To increase shareholder’s equity, you can either 1) increase capital stock by raising more money or 2) increase profits (this will increase retained earnings since this equals sum of profits - sum of dividends. To decrease shareholder’s equity, you can either 1) decrease profits or 2) pay out dividends.

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84
Q

Type of company valuations? (5) Describe them.

A
  1. Book valuation - Total assets - total liabilities - debt
  2. Liquidation valuation - if company was liquidated today (using assumptions of fixed/variable costs of products)
  3. Price-multiple valuation - share price x # of shares x multiple of similar company
  4. Market valuation - whatever market will pay
  5. Discounted cash flow - Estimate all future cash (stock sold, dividends paid, etc) and figure out “net present value” - assume with discount rate
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5
Perfectly
85
Q

What is the NIA-AA Dementia staging system? What are the 6 stages and what functions are associated with them?

A

1 - Cognitively unimpaired - Performance in expected range
2 -Cognitively unimpaired - Performance in expected range and subjective decline; newly acquired neurobehavioral symptoms
3 - Mild cognitive impairment (MCI) - Performance in impaired range, cognitive decline from baseline in any domain, ADLs independent, but may be less efficient
4- Mild dementia - Substantial cognitive impairment affecting several domains and clearly evident functional impact on daily life, no longer fully independent
5- Moderate dementia - More severe form than 4
6 Severe dementia - More sever form than 5

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86
Q

What Allergan company acquisition in 2015 was not fruitful for depression?

A

Allergan bought Naurex for $560M upfront payment for repastinel (NMDA drug) for MDD, but this failed 3 Phase 3 clinical trials in 2019.

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87
Q

How can you automate the window discriminator method?

A

Can cluster spikes automatically into groups based on shape - shape of spike is characterized b features extracted using wavelets or principal component analysis (PCA).

88
Q

What are the 6 molecular steps that happen in AD neurons?

A
  1. APP is cleaved and Abeta formed in the membrane of neurons
  2. Abeta oligomers form extracellulary and start to cause synaptic dysfunction
  3. Fibrils of amyloid beta oligomers aggregate into plaques which interfere with function of neurons
  4. Amyloid beta deposits outside cells and in blood vessels of the brain which activate immune cells
  5. Misfolded tau aggregates into neurofibrillary tangles inside neurons, displacing intracellular organelles.
  6. Misfolded tau is transmitted across synapses and catalzyes further misfolding of tau
89
Q

What is the average depth of the SF bay? How deep and where is the deepest point?

A

15 ft. The deepest point is 300ft underneath the Golden Gate bridge

90
Q

What is TMS? What are the advantages?

A

Transcranial magnetic stimulation - Neural stimulation technique that can stimulate 1000s of neurons with electrical current 3.5mm deep into the cortex that are directly next to magnetic coiled device placed on the skull

91
Q

What are net sales and when does it get recorded on income statement?

A

Total amount company will collect from sale, gets recorded when product is shipped and becomes an “account receivable”

92
Q

What are percentages that company agreed on different multiples for liquidation preference during 1st round of financing?

A

78% agreed to 1x liquidation preference, 9% agreed to 1.1-2x, 5% agreed to 2.1-3x and 8% agreed to >3x.

93
Q

How to handle disagreeing with lead investor?

A

Say you are a passive investor

94
Q

What is a spectral feature and how is it created?

A

EEG, ECoG or other recorder extracts signal, power spectrum is computed with FFT to yield a particular frequency which is the “spectral feature”. For example, motor movement or imagery will reduce power in alpha frequency band (8-12 Hz), so use power in alpha band as a feature in BCI to allow subject to move cursor.

95
Q

What counts as assets?

A

Everything you got - cash in the bank, inventory, machines, buildings, etc. Also includes certain “rights” you own - customers who owe money. Assets must be quantifiable.

96
Q

Who is Nora Ephron, what are 3 of her famous movies?

A

Writer of movies. Silkwood, Sleepless in Seattle, When Harry met Sally

97
Q

What is frequency and angular frequency?

A

Frequency is an oscillation over a time period, angular frequency is 2pi x frequency

98
Q

What is the equation of fractal dimension and how does it relate to EEG?

A

D = 1-2; 1-For simple curves, 2- More irregular curves. EEG is typically between 1.4-1.7 with 1.7 meaning higher spiky activity such as seizures

99
Q

What are the two types of silicon based microelectrode arrays and why are they better than microwire arrays?

A

Michigan and Utah arrays, they record all along the length of the electrode, rather than just at tips, increasing density and spatial resolution compared to microwire arrays.

100
Q

How many blowholes does a gray whale have? What shape and how high are its spout?

A

A gray whale has 2 blowholes, spouts up in a heart shaped pattern 5 feet in the air. The bigger the whale the higher the spout

101
Q

What JNJ drug for depression got approved in 2019?

A

JNJ’s esketamine (Spravato), a nasal formulation of ketamine, got approved for MDD.

102
Q

What does the term “accounts receivable” mean?

A

Obligation of customers to pay the company for goods shipped to them on credit.

103
Q

What are the genetics in neuroinflammation in AD?

A

CD33 switches on pro-inflammatory state, whereas TREM2 switches it off (just about every pharma company has started a CD33 program)

104
Q

What are the sources (2) and uses (4) of cash and give an example for each?

A

Sources - money coming in: 1. Operating activities (When a customer pays) 2. Financial (When money is borrowed or stock is sold); Uses - money going out: 1. Operating activities (when suppliers are paid) 2. Financial (when debt is payed on a loan or dividends are paid) 3. Capital investments (long lived productive assets) 4. Income taxes - paid to government

105
Q

Who is Martha Graham, what did she do and during what time period?

A

Martha Graham (May 11, 1894-April 1, 1991) was an American modern dancer and choreographer. Her style, the Graham technique, reshaped American dance and is still taught worldwide.

106
Q

What is inventory valuation worksheet and what does it contain?

A

Detailed listings of where inventory is in the process. Includes Raw materials inventory, in-work-process inventory, and finished goods inventory.

107
Q

Cadent Therapeutics

A

Cadent Therapeutics is using allosteric modulators and will move 2 drugs into 3 Phase 2 clinical trials in 2019 - targeting SK channels for Essential tremor and spinocerebellar ataxia and targeting NMDA receptors for depression (entering Phase 1) and schizophrenia (preclinical)

108
Q

What is an instrument landing system (ILS)? Where does it operate from? What types of signals (2) does it provide?

A

ILS is a ground-based instrument that provides lateral and vertical guidance to an aircraft approaching and landing on a runway. It uses combination of radio signals and high-intensity lighting arrays to enable a safe landing.

109
Q

What is equation for income from operations or (Loss)?

A

Sales - cost & expenses OR Gross margin - expenses

110
Q

What are “the books” in finance? (2) Describe each

A

Journals - chronological recording of all financial events (nothing is missing from here)
Ledgers - grouping of items that we want to keep track of; for ex. all “Accounts receivable”

111
Q

What is the balance sheet equation?

A

Assets = Liabilities + Worth

112
Q

What is a form factor?

A

As aspect of hardware design which defines and prescribes the size, shape, and other physical specifications of components, particularly in consumer electronics and electronic packaging. A form factor may represent a broad class of similarly sized components or it may prescribe a specific standard.

113
Q

Cash balance on ledger is same as what?

A

Cash balance on balance sheet

114
Q

How much does the government make a human life worth?

A

$9.1M (2019)

115
Q

What are 2 terms that are equal between financial statements (2 sets)?

A

Cash flow statement “Ending cash balance” bottom line = Balance sheet “Cash” top line; Total assets = Total liabilities on balance sheet

116
Q

What is in a whale’s spout? What can you collect from it?

A

A whale’s spout contains snot and scientists collect it with drones for DNA of whales

117
Q

What are delta and theta waves? What frequency? What functions are they involved in?

A

0.5-4Hz (Delta) and 4-8Hz (theta) waves that are present during deep sleep or inactivity or meditation

118
Q

What is the rule of 70?

A

The number of years for value to double (dollar to double)= 70/Rate of change

119
Q

What is Neuropace? When was it approved and for what indication?

A

Device has a neurostimulator which is battery powered and surgically implanted in the brain that is programmed with closed loop stimulation, it contains “leads” which are wires with electrodes attached to measure activity. Device approved for drug resistant epilepsy patients with focal seizures. Approved in December 2018.

120
Q

What is an AutoRegression model (AR) and how is it used for brain signals?

A

Predicting signal based on past measurements, For brain signals - since non-stationary, need to apply time varying coefficient so to capture local statistical structure of signal over time (can use these features for future processing ex. classification)

121
Q

What are “Current Assets” and what are the 4 categories?

A

Assets that are expected to be converted into cash in <12 months. Cash, Accounts receivable, Inventory, Prepaid Expenses

122
Q

What is “sale of stock”?

A

The exchange of cash for stock certificate/shares

123
Q

What are the 3 financial statements?

A

Balance sheet, Income statement, Cash flow statement

124
Q

What are liabilities? What are the 3 types of liabilities?

A

Economic obligations of enterprise to lenders, supplier, employees, etc

  1. Current liabilities
  2. Long-term debt
  3. Shareholder’s equity
125
Q

What are current liabilities and what are the 4 types?

A

Current liabilities must be paid within 12 months

  1. Accounts payable - payments owed to suppliers
  2. Accrued expenses - payments owed to employees and others for services
  3. Current debt - Debt owed in 12 months
  4. Income taxes - taxes on profit
126
Q

What are the 5 stages of Alzheimer’s progression? When does MCI and dementia happen during these stages?

A
  1. Abeta accumulates
  2. Tau accumulates
  3. Brain structural changes (MCI happens years after brain structural changes happen and memory impairment starts)
  4. Memory impairment
  5. Functional impairment (Dementia occurs here)
127
Q

What are the 2 steps of the investment cycle and what terms on the financial statements change?

A
  1. Net borrowings on cash flow statement change, this changes cash on balance sheet and debt on balance sheet (if paid within 12 months -current liabilities, if paid afterwards - long term debt). 2. Sale of capital stock on cash flow statement increases along with cash and capital stock on the balance sheet.
128
Q

What is EEG? What are its advantages over other techniques?

A

Electroencephalography - Non-invasive technique for recording electrical activity using electrodes placed on the scalp. EEG measures summation of polysynaptic potentials (1000s of neurons at a time). Great temporal resolution (ms range), but poor spatial resolution (square cm)

129
Q

What is “working capital”? What is another term?

A

Current assets - Current liabilities; Also called “net current assets or funds”

130
Q

What is Capital Stock?

A

Capital stock is original money to start and any add-on money invested in the business that is represented by shares of capital stock held by owners of the enterprise, can be either common shares or preferred shares

131
Q

Akili Interactive

A

Digital therapeutic for pediatric ADHD (currently being reviewed by FDA) and feasibility study in ASD just completed

132
Q

What ions are at greater concentrations inside/outside neurons? What is the resulting membrane potential?

A

Neurons have a larger concentration of Na, Cl, and Ca on outside of cell and greater concentration of K and organic anions (A-) on inside resulting in potential difference of -70 mV across the neuron’s membrane when at rest.

133
Q

Axovant programs (2019)

A

AXO-LENTI-PD (TH/AADC/CH1) - lenti virus for PD - Phase 1/2; AXO-AAV-GM1 (GLB1) - GM1 Gangliodosis; AXO-AAV-GM2 (HEXA/HEXB) - GM2 Gangliodosis/Tay Sachs; (all clinical programs) AXO-AAV-OPMD (PABPN1) - Ocularpharyngeal muscular dystrophy, AXO-AAV-ALS/FTD (C9ORG72) - ALS and FTD (preclinical programs)

134
Q

What is a tender offer?

A

An offer to purchase some or all of a shareholder’s shares in a corporation (price offered is usually at a premium to market price and requires condition of at least 51% of the shares); often called a takeover bid

135
Q

What are the 3 products costs?

A
  1. Raw materials
  2. Direct labor
  3. Overhead costs
136
Q

What are the 3 financial terms that are the “bottom line”?

A

Income, Profit, Earnings

137
Q

What is the link between Abeta/APOE4/mGluR5/PIP2/PrP (3)

A
  1. APOE4 and Abeta have been shown to interfere with PIP2 metabolism.
  2. Abeta oligomers bind to mGluR5 and co-receptor PrP, blocking mGluR5 can improve cognition in AD mouse model
  3. Nanomolar concentrations of Abeta oligomers can bind mGluR5, causing hydrolysis of PIP2 at the presynaptic terminal and reduce release probability of synapses in early AD
138
Q

What is Tasigna (other name)?

A

Nilotinib - Novartis’s approved drug for CML now in a Phase 2 for PD (Elevated levels of DOPAC and HVA and increased TREM-2 levels in CSF) in interim study (2019)

139
Q

1 mile conversion to km?

A

1 mile = 1.6 km

140
Q

What is Neuropace? When was it approved and for what indication?

A

Device has a neurostimulator which is battery powered and surgically implanted in the brain that is programmed with closed loop stimulation, it contains “leads” which are wires with electrodes attached to measure activity. Device approved for drug resistant epilepsy patients with focal seizures. Approved in December 2018.

141
Q

What are the 2 types of non-current assets?

A

Other assets (intangible assets such as patents, trade names) and fixed assets (buildings, machinery, other illiquid assets, PP&E - property, plant and equipment)

142
Q

How are voting rights defined

A

Defines how the preferred stock and the common stock relate to each other in the context of a share vote.

143
Q

What do you need to do to stay in balance if you add to an asset account (1/2 things)?

A

If you add an asset, you need to either subtract another asset, or add to liabilities

144
Q

What are the 3 types of microelectrode arrays?

A

Microwire, silicon-based, and flexible array

145
Q

What are the 4 steps of the sale cycle and what terms on the financial statements change?

A
  1. Net sales on income statement changes which affects Net income and Retained earnings on the balance sheet; Also place in Accounts receivable in balance sheet 2. When purchase is made, inventory on balance sheet moves to COGS on income statement 3. When sale is made, accounts receivable becomes cash receipts on cash flow statement 4. Net income is generated and added to retained earnings on balance sheet
146
Q

Explain the financial statement terms that change for Asset purchases/depreciation?

A
  1. Change PP&E on Cash flow statement, increase cash on balance sheet and add to fixed costs on balance sheet. 2. Expenses on income statement increase resulting in increased accumulated depreciation on balance sheet
147
Q

What is zhug (schoog) (6 ingredients)? Where is it from?

A

Zhug is a hot sauce made from fresh red or green hot peppers seasoned with coriander, garlic, salt, black cumin and various spices. From Yemen.

148
Q

What is the biggest mountain on each continent?

A

Mt. Everest (Asia), Aconcagua (South America), Denali (McKinley) (North America), Kilamanjaro (Africa), Elbrus (Europe), Vinson Massif (Antarctica), Kosciusko (Australia)

149
Q

What are cash disbursements (2 terms)? What term does it affect?

A

Cash disbursements (also called “payments” or “disbursements”) - cash spent to pay for rent, inventory and supplies or for workers salary; This makes “accounts payable” lower on income sheet

150
Q

What is a no-shop agreement? How long does it normally last? What might they have a carve out option for?

A

Company cannot solicit, initiate, encourage or assist submission of any proposal, negotiation or offer from other entities and 2) can’t enter into any discussions or negotiations or execute any agreement. Usually 45-60 days. Can make a carve-out for acquisitions

151
Q

Learning how to learn: What 4 things should you do in the preparation phase?

A
  1. Identify goal
  2. Create reward
  3. Choose testing condition
  4. Identify resources
152
Q

What is a cash transaction?

A

A transaction where cash is exchanged (changes hands)

153
Q

How tall is Mount Everest, who first climbed it and when and where is it located?

A

29,028ft, Edmund Hillary and Tenzing were first to climb it in 1953, located on border of Nepal and China

154
Q

What is a Fourier series or Fourier expansion?

A

Time varying signal expansion into a sum of infinite terms.

155
Q

3 Key components to remember when creating a capitalization table?

A

Timing, burn rate, milestones
Timing - General rule is funding rounds are separated by 12-18 months (plan for 6-12 months to raise round)
Burn rate - know your burn rate
Milestones - think of milestones as reduction or risk

156
Q

What are the 2 steps of the expense cycle and what terms on the financial statements change?

A
  1. Expenses increase on income statement and become account payable on balance sheet, changing net income and retained earnings on balance sheet 2. When money is paid, Account payable on balance sheet becomes cash disbursements on cash flow statement which changes cash on balance sheet
157
Q

Voyager Therapeutics/AbbVie deal

A

$69M upfront payment from AbbVie for AAV tau program

158
Q

How much did Cortexyme raise and from whom (8) in May 2018?

A

Cortexyme raised a $76M Series B led by Pfizer and Takeda Ventures with participation from Lamond family, Dolby Family Ventures, Sequoia Capital, Vulcan, Breakout labs and Verily

159
Q

How are assets grouped?

A

From liquid to illiquid assets: Cash and securities, assets for sale: inventory, productive assets: plant and machinery. Fixed assets are normally least liquid.

160
Q

What are gamma waves? What frequency? What functions are they involved in?

A

30-100Hz waves found in attention, perception, memory; indicate simultaneous processing of information from different brain areas and are associated with higher states of conscious perception

161
Q

What is the link between Down Syndrome and AD?

A

People with Down Syndrome get early onset AD, due to their extra copy of APP gene (caused by chromosome 21 trisomy)

162
Q

What is spike sorting?

A

Spike sorting is the signal processing method to reliably isolate and extract the spikes being emitted by a single neuron per electrode; allow spikes to be extracted from hash.

163
Q

What is tamarind and what parts (3) of it are used? Which parts are used for what?

A

Edible pulp is used in cuisines, traditional medicine and metal polish. Its wood is used for woodworking. Its leaves are used in Indian cuisine.

164
Q

What is the equation for “Ending cash balance”?

A

Ending cash balance = Beginning cash balance + Cash from operations - Fixed asset purchases + Net borrowings - Income taxes paid + Sale of stock

165
Q

What is an income statement and what are 3 other names?

A

Income statement gives information about a company’s profitability. Reports what is sold - costs to make - selling and general expenses = income (all for a period). Called “Profit and loss statement”, “Earnings statement” or “P&L”

166
Q

What are operating expenses (3) and what is another name?

A

Sales and marketing, R&D, General and Administrative (G&A); Also called SG&A

167
Q

What is PET? What are its advantages?

A

Positron Electron Tomography - Measures activity through metabolic activity of brain by injecting radiotracer (radio-labeled molecule - usually glucose) into bloodstream and detects what regions are taken up in the brain. Disadvantages - need injected radiotracer and these tend to have low half-life.

168
Q

What is the average time a person lives with diagnosis of AD?

A

8-10 years

169
Q

How does income statement effect balance sheet?

A

If income statement shows income, then retained earnings are increased on balance sheet.

170
Q

What are the two financial terms for the “top line”

A

Sales and Revenue

171
Q

Who currently has AAV candidates (Mar 2019) (4)?

A

Avexis, Nightstar, Voyager, Spark

172
Q

What brain functions are gamma oscillations used for and what are they sensitive to?

A

Perception, memory, and attention. Sensitive to metabolic and oxidative stress.

173
Q

What is Transcranial ultrasound? What are the advantages?

A

Transcranial ultrasound is a neural stimulation technique that can stimulate 1000s of neurons by using low-frequency ultrasound waves. Can penetrate deeper into the brain.

174
Q

What is sales - cost of goods sold called? (3 names)

A

Gross margin, gross profit, manufacturing margin

175
Q

What does inventories on balance sheet include? (2)

A
  1. Overhead 2. Depreciation
176
Q

What is an epiphyte? Give 3 examples? Where do they grow?

A

A plant that grows on another plant that is not parasitic. Ferns, Air plants, and orchids. They grow on tree trunks in tropical rainforests.

177
Q

What is DegenRx, how much did they raise from who?

A

DegenRx raised $20M Series A from Swanbridge and BOM Brabant Ventures. They are developing vector based therapies for AD and PD.

178
Q

What is an agouti? What genus and where are they found (2)?

A

The term agouti designates several rodent species of the genus, Dasyprocta. They are found in Central and South America.

179
Q

What is non-operating income or expense?

A

Non-operating income/expense - receiving interest in the company’s bank account or paying interest on a loan (reported just below “Income from operations”

180
Q

What are the three types of assets that sum up to total assets?

A
  1. Current Assets
  2. Other assets (intangible assets)
  3. Net fixed assets
181
Q

Who is Vince Gilligan?

A

Writer of Breaking Bad

182
Q

What is Discrete Fourier transform?

A

This applies to a discretely sampled signal over a certain time interval.

183
Q

What is a microelectrode, what is it made of? What does it measure?

A

Made of tungsten or paladium-iridium alloy, electrode is insulated except for very tip (1 uM diameter). These record extracellular signaling of neurons, the negative outflux of ions after an action potential.

184
Q

What is UPDRS? What is it composed of (3) and what is total score?

A

Unified Parkinson’s Disease Rating Scale - scoring of e categories on 1-4 scale: Mentation, behavior and mood, Daily living activities, and motor function, possible score of 108 (higher is worse).

185
Q

What is a wavelet transform? What are wavelets translated from?

A

Represents signals that are non periodic or have sharp discontinuities (unlike sin and cosines in Fourier analysis), Uses finite basis functions called wavelets which are scaled and translated from a single finite waveform known as mother wavelet

186
Q

What term does changing net income also change?

A

Retained earnings on balance sheet

187
Q

What is viral evidence in AD (3)?

A
  1. HHV-6A and HHV-7 is found in postmortem AD brains (Joel Dudley)
  2. HHV-6 and HSV-1 can seed abeta in 3D cultures of human neurons (Rudy Tanzi)
  3. HSV infection increases risk of developing the condition, Antivirals made people 10x less likely to develop AD (Taiwan group)
188
Q

What was the Neurocrine/Voyager deal in Feb 2019?

A

Neurocrine paid Voyager $165M upfront payment for option for VY-AADC gene therapy (currently in Phase 2). Opt in after Phase 2 data where they will split costs/profits 50/50

189
Q

What are beta waves? What frequency? What functions are they involved in?

A

12-30Hz waves that can be measured over parietal or frontal regions during periods of great concentration and attention towards cognitive tasks; indicates alertness, attentiveness, and engagement in problem solving or decision making

190
Q

Mnemonics (#1-10)

A
  1. Gun
  2. Shoe
  3. Tree
  4. Floor
  5. Hive
  6. Sticks
  7. Heaven
  8. Gate
  9. Shine
  10. Hen
191
Q

What is thromboplebitis?

A

Life threatening altitude induced blood clot

192
Q

Li Huei Tsai’s work (2019)

A

Auditory and light-induced gamma oscillations in the CA1 of the hippocampus and auditory cortex caused abeta removal and microglial activation and improves memory of mouse models of AD (GENUS) - gamma entertainment using sensory stimuli

193
Q

What is MEG? What is this activity measured by? What are its advantages over other techniques?

A

Megnetoencephalography - Non-invasive device that measures magnetic waves produced by electrical activity of neurons. Measured using superconducting quantum interface devices. Has great spatial and temporal resolution, but can only measure neurons that run in similar orientation, therefore most likely recording perpendicular to cortical surface (most likely concurrent activity of pyramidal neurons in neocortex)

194
Q

What in Inventory and what are the 3 types?

A

Inventory includes both products ready for sale to customers and also materials to be made into products.

  1. Raw materials inventory - Materials to make product
  2. In-work-process inventory - Materials currently in manufacturing partially finished
  3. Finished goods inventory - Finished products ready to be shipped to customer
195
Q

Why does EEG measure oscillatory activity?

A

Because it records thousands of neurons at a time, so it can only capture correlated activities of large populations of neurons

196
Q

What is the percentage of MCI patients that develop dementia each year?

A

10-15%

197
Q

What is the basic idea behind Fourier analysis? How can you approximate a step function using Fourier analysis?

A

To decompose a signal into a weighted sum of sin and cosine waves of different frequencies. Approximate by adding waves of different frequencies each weighted by different amplitude - each amplitude is decomposed at individual frequencies.

198
Q

What is “prepaid expenses” in the current assets section?

A

Expenses paid that services are not yet rendered (rent, insurance, etc)

199
Q

What is fractal dimension?

A

Quantitative measure of self-similarity (parts of signals resembling the whole and this similarity repeating in a recursive fashion)

200
Q

What are cash receipts (2 terms)? What term does it affect?

A

Cash receipts (also called “collections” or “receipts”) - cash from collecting money from customers; This makes “accounts receivable” lower on income sheet

201
Q

Solvency vs. profitability

A

Solvency is when you have enough cash to pay for bills, profitability is when your revenue is more than your costs (you can be profitable, but not solvent).

202
Q

What are the current treatments and its effect on disease?

A

Donepezil (Aricept) and Memantine (Delay of worsening of symptoms by 6-12 months)

203
Q

What is a way to identify (1) and utilize (1) a spectral feature?

A

Identify: Ask subject to perform motor movement and find these frequency bands to utilize in BCI experiments involved with movement. Utilize: Bank spectral features and allow learning algorithm to automatically select features that enhance classification on test data.

204
Q

What are the mutations in APOE variants and what are percentages of different types in AD patients?

A

APOE2 (4% of AD patients) has 2 cysteine residues at position 112 and 158, APOE3 (59% of AD patients) has a cysteine at 112 and an arginine at 158 and APOE4 (37% of AD patients)has two arginines at 112 and 158

205
Q

How do you calculate your actual wealth taking into account inflation?

A

Real wealth = (Nominal wealth + rate change)/(Consumption + inflation)

206
Q

Neurocrine Biosciences programs (2019)

A

Ingrezza (Valbenazine) - vesicular monamine transporter 2 inhibitor for tardive dyskinesia, opicapone in Phase 3 for PD, drug for CAH (Congenital adrenal hyperplasia), Phase 1 VMAT2 drug for neurology/psychiatry indication

207
Q

Who normally becomes the shareholder representative?

A

Usually an executive from the seller or one of the VC board members

208
Q

Where is APOE expressed?

A

In CNS, APOE is expressed in astrocytes, microglia, and neurons in stressed conditions.

209
Q

What spaceship was Neil Armstrong on? (First to walk on the moon) What series were before Apollo?

A

Apollo 11 (Gemini were before Apollo)

210
Q

What is the function of BAG? How is it differentially regulated in AD to affect certain neurons? Who’s lab

A

Bcl-associated athanogene 3 (BAG) (protein reduction in AD brains) - can clear tau through protein homeostasis process. Excitatory neurons are more vulnerable to tau pathology compared to inhibitory neurons due to reduction of BAG expression. Karen Duff - Columbia Univeristy

211
Q

What is a shareholder representative?

A

A representative of all former shareholders that deals with all the issues between buyer and seller after the transaction (acquisition)

212
Q

What are net fixed assets? What is another name for net fixed asset?

A

Fixed assets (at cost when bought) - accumulated depreciation. Another name is “book value of an asset”

213
Q

What did Leonardo de Vinci paint (3)?

A

Mona Lisa, Vitruvius Man, Last Supper

214
Q

When is humpback whaling migration in California? What about gray whales?

A

Humpback: April to December, migrate from Alaska to Hawaii; Gray whales: November to April

215
Q

What is DOPAC and HVA?

A

Dihydroxyphenylacetic acid and homovanillic acid - metabolized by dopamine - can be found in CSF as readout of dopamine activity in the brain

216
Q

Actinogen, what are they devloping and in what phase?

A

Inhibiting 11b-HSD1 which lowers cortisol levels. Phase 2 for AD.

alzheimer's disease (science) (5 decks)

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